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1.
BMC Med ; 18(1): 5, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31918762

RESUMO

BACKGROUND: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. METHODS: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. RESULTS: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. CONCLUSION: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.

2.
Int J Cancer ; 146(3): 759-768, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30968961

RESUMO

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.

3.
J Safety Res ; 70: 159-167, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31847991

RESUMO

INTRODUCTION: Responsibility analysis allows the evaluation of crash risk factors from crash data only, but requires a reliable responsibility assessment. The aim of the present study is to predict expert responsibility attribution (considered as a gold-standard) from explanatory variables available in crash data routinely recorded by the police, according to a data-driven process with explicit rules. METHOD: Driver responsibility was assessed by experts using all information contained in police reports for a sample of about 5000 injury crashes that occurred in France in 2011. Three statistical methods were used to predict expert responsibility attribution: logistic regression with L1 penalty, random forests, and boosting. Potential predictors of expert attribution referred to inappropriate driver actions and to external conditions at the time of the crash. Logistic regression was chosen to construct a score to assess responsibility for drivers and riders in crashes involving one or more motor vehicles, or involving a cyclist or pedestrian. RESULTS: Cross-validation showed that our tool can predict expert responsibility assessments on new data sets. In addition, responsibility analyses performed using either the expert responsibility or our predicted responsibility return similar odds ratios. Our scoring process can then be used to reliably assess responsibility based on national police report databases, provided that they include the information needed to construct the score.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31767565

RESUMO

BACKGROUND: Diet has been recognized as a modifiable risk factor for breast cancer. Highlighting predictive diet-related biomarkers would be of great public health relevance to identify at-risk subjects. The aim of this exploratory study was to select diet-related metabolites discriminating women at higher risk of breast cancer using untargeted metabolomics. METHODS: Baseline plasma samples of 200 incident breast cancer cases and matched controls, from a nested case-control study within the SU.VI.MAX cohort, were analysed by untargeted LC-MS. Diet-related metabolites were identified by partial correlation with dietary exposures, and best predictors of breast cancer risk were then selected by Elastic Net penalized regression. The selection stability was assessed using bootstrap resampling. RESULTS: 595 ions were selected as candidate diet-related metabolites. 14 of them were selected by Elastic Net regression as breast cancer risk discriminant ions. A lower level of piperine (a compound from pepper) and higher levels of AcetylTributylCitrate (an alternative plasticizer to phthalates), pregnene-triol sulfate (a steroid sulfate) and 2-amino-4-cyano butanoic acid (a metabolite linked to microbiota metabolism) were observed in plasma from women who subsequently developed breast cancer. This metabolomic signature was related to several dietary exposures such as a "Western" dietary pattern and higher alcohol and coffee intakes. CONCLUSIONS: Our study suggested a diet-related plasma metabolic signature involving exogenous, steroid metabolites and microbiota-related compounds associated with long-term breast cancer risk that should be confirmed in large-scale independent studies. IMPACT: These results could help to identify healthy women at higher risk of breast cancer and improve the understanding of nutrition and health relationship.

5.
Int J Cancer ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31652358

RESUMO

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR1-SD ]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR1-SD : 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR1-SD : 1.16; 95% CI 1.01; 1.35), pancreatic (HR1-SD : 1.37; 95% CI 1.13; 1.66), thyroid (HR1-SD : 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR1-SD : 1.17; 95% CI 1.11; 1.22) and endometrial (HR1-SD : 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.

6.
JAMA Intern Med ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479109

RESUMO

Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. Main Outcomes and Measures: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio [HR], 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001). Conclusions and Relevance: This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.

7.
Am J Clin Nutr ; 110(6): 1424-1433, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31559413

RESUMO

BACKGROUND: Processed meat intake is associated with a higher risk of colorectal and stomach cancers, coronary artery disease, and type 2 diabetes and with higher mortality, but the estimation of intake of different processed meat products in this heterogeneous food group in epidemiological studies remains challenging. OBJECTIVE: This work aimed at identifying novel biomarkers for processed meat intake using metabolomics. METHODS: An untargeted, multi-tiered metabolomics approach based on LC-MS was applied to 33 meat products digested in vitro and secondly to urine and plasma samples from a randomized crossover dietary intervention in which 12 volunteers consumed successively 3 processed meat products (bacon, salami, and hot dog) and 2 other foods used as controls, over 3 consecutive days. The putative biomarkers were then measured in urine from 474 subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study for which detailed 24-h dietary recalls and FFQs were available. RESULTS: Syringol and 4 derivatives of syringol were found to be characteristic of in vitro digests of smoked meat products. The same compounds present as sulfate esters in urine increased at 2 and 12 h after consumption of smoked meat products (hot dog, bacon) in the intervention study. The same syringol sulfates were also positively associated with recent or habitual consumption of smoked meat products in urine samples from participants of the EPIC cross-sectional study. These compounds showed good discriminative ability for smoked meat intake with receiver operator characteristic areas under the curve ranging from 0.78 to 0.86 and 0.74 to 0.79 for short-term and habitual intake, respectively. CONCLUSIONS: Four novel syringol sulfates were identified as potential biomarkers of smoked meat intake and may be used to improve assessment of smoked meat intake in epidemiological studies. This trial was registered at clinicaltrials.gov as NCT03354130.

8.
BMC Med ; 17(1): 178, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31547832

RESUMO

BACKGROUND: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. METHODS: A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. RESULTS: Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70-0.90), asparagine (OR = 0.83 (0.74-0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76-0.90)), aa C36:3 (OR = 0.84 (0.77-0.93)), ae C34:2 (OR = 0.85 (0.78-0.94)), ae C36:2 (OR = 0.85 (0.78-0.88)), and ae C38:2 (OR = 0.84 (0.76-0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11-1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06-1.24)) and PC ae C36:3 (OR = 0.88 (0.82-0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. CONCLUSIONS: These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

9.
Eur J Epidemiol ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31564045

RESUMO

Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants' shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e-09) and 0.77 (0.72, 0.82; ptrend = 1.7e-15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.

10.
Int J Cancer ; 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31187481

RESUMO

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case-cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case-control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m2 compared to women with BMI 18.5-25 kg/m2 , the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05-2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43-2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11-2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68-1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity-breast cancer relationship but does not explain all of the association.

11.
Stat Med ; 38(14): 2680-2703, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30873639

RESUMO

Graphical models are used in many applications such as medical diagnostics and computer security. Increasingly often, the estimation of such models has to be performed on several predefined strata of the whole population. For instance, in epidemiology and clinical research, strata are often defined according to age, gender, treatment, or disease type. In this article, we propose new approaches dedicated to the estimation of binary graphical models on such strata. These approaches are implemented by combining well-known methods that have been developed in the context of a single binary graphical model, with penalties encouraging structured sparsity, which have recently been shown to be appropriate when dealing with stratified data. Empirical comparisons on synthetic data highlight that our approaches generally outperform its competitors. We present an application of the approach to study associations among the injuries suffered by victims of road accidents according to road user type.

12.
Breast Cancer Res ; 20(1): 147, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509329

RESUMO

BACKGROUND: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction. METHODS: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women's Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention. RESULTS: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10- 6 for ModelER+ and 3.0 × 10- 6 for ModelGail. CONCLUSIONS: Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/diagnóstico , Modelos Biológicos , Receptores Estrogênicos/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
13.
Am J Clin Nutr ; 108(1): 117-126, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29924298

RESUMO

Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors. Objective: In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed. Results: The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively. Conclusions: This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.


Assuntos
Carcinoma Hepatocelular/etiologia , Estilo de Vida Saudável , Neoplasias Hepáticas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Estudos de Casos e Controles , Estudos de Coortes , Inquéritos sobre Dietas , Europa (Continente)/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Cancer Epidemiol Biomarkers Prev ; 27(5): 531-540, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29563134

RESUMO

Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites.Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk.Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%.Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators. Cancer Epidemiol Biomarkers Prev; 27(5); 531-40. ©2018 AACR.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/epidemiologia , Estilo de Vida , Neoplasias Hepáticas/epidemiologia , Metaboloma , Idoso , Biomarcadores Tumorais/metabolismo , Índice de Massa Corporal , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/prevenção & controle , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/prevenção & controle , Masculino , Metabolômica , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
15.
PLoS One ; 12(11): e0187320, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29117206

RESUMO

INTRODUCTION: This research aims to estimate the relative risks of responsibility for a fatal accident linked to driving under the influence of cannabis or alcohol, the prevalence of these influences among drivers and the corresponding attributable risk ratios. A secondary goal is to estimate the same items for three other groups of illicit drugs (amphetamines, cocaine and opiates), and to compare the results to a similar study carried out in France between 2001 and 2003. METHODOLOGY: Police procedures for fatal accidents in Metropolitan France during 2011 were analyzed and 300 characteristics encoded to provide a database of 4,059 drivers. Information on alcohol and four groups of illicit drugs derived from tests for positivity and potential confirmation through blood analysis. The study compares drivers responsible for causing the accident, that is to say having directly contributed to its occurrence, to drivers involved in an accident for which they were not responsible, and who can be assimilated to drivers in general. RESULTS: The proportion of persons driving under the influence of alcohol is estimated at 2.1% (95% CI: 1.4-2.8) and under the influence of cannabis at 3.4% (2.9%-3.9%). Drivers under the influence of alcohol are 17.8 times (12.1-26.1) more likely to be responsible for a fatal accident, and the proportion of fatal accidents which would be prevented if no drivers ever exceeded the legal limit for alcohol is estimated at 27.7% (26.0%-29.4%). Drivers under the influence of cannabis multiply their risk of being responsible for causing a fatal accident by 1.65 (1.16-2.34), and the proportion of fatal accidents which would be prevented if no drivers ever drove under the influence of cannabis is estimated at 4.2% (3.7%-4.8%). An increased risk linked to opiate use has also been found to be significant, but with low prevalence, requiring caution in interpreting this finding. Other groups of narcotics have even lower prevalence, and the associated extra risks cannot be assessed. CONCLUSION: Almost a decade separates the present study from a similar one previously conducted in France, and there have been numerous developments in the intervening years. Even so, the prevalence of drivers responsible for causing fatal accidents under the influence of alcohol or narcotics has stayed remarkably stable, as have the proportion of fatal accidents which could in theory be prevented if no drivers ever exceeded the legal limits. The overall number of deaths from traffic accidents has dropped sharply during this period, and the number of victims attributable to alcohol and/or cannabis declined proportionally. Alcohol remains the main problem in France. It is just as important to note that one in two drivers considered to be under the influence of cannabis was also under the influence of alcohol. With risks cumulating between the two, it is particularly important to point out the danger of consuming them together.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Cannabis/efeitos adversos , Etanol/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Condução de Veículo/estatística & dados numéricos , Dirigir sob a Influência/estatística & dados numéricos , Etanol/sangue , França/epidemiologia , Humanos , Razão de Chances , Prevalência , Fatores de Risco
16.
17.
PLoS One ; 11(11): e0167082, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27893865

RESUMO

BACKGROUND: Since 2002, France has been strengthening legislation on road traffic. This study is intended to evaluate the changes in Traumatic Brain Injury (TBI) incidence and mortality resulting from Road Traffic Collision (RTC) in the two 6-year periods before and after 2002. METHODS: We used a Registry of all RTC casualties in the Rhône Department of France. Each casualty was coded according to the Abbreviated Injury Scale (AIS). The study describes changes in demographic variables, TBI (AIS ≥ 2) incidence and mortality, other body lesions (AIS ≥ 3) associated with TBI, road user types, seatbelt and helmet wearing. FINDINGS: RTC casualty occurrences decreased by 21% (from 64,312 to 50,746) during the period after 2002. TBI occurrence accounted for 8.6% and 6.7% of all RTC in both periods. This corresponds to a reduction of TBI casualty incidence (-42%), which was much more pronounced than RTC casualty incidence (-25%) (p < 0.0001). Severe and critical TBI (AIS-4 and -5) incidences were reduced by half as much (-21%), compared to TBI incidence. TBI mortality rate (among population) and lethality (among TBI related to RTC casualties) decreased 56% and 23%, respectively. This reduction particularly affected car occupants and victims who deceased. TBI incidence decreased 43% in all 10-year age classes until 60 on average, this decrease declining with age in the period after 2002. After adjustment for age, sex, road user types, and severity of lesions at the head and other body regions, logistic regression analysis displayed a protective effect of the period following 2002, on the risk of death after RTC-related TBI. INTERPRETATION: The greater reductions in the incidence, severity and mortality of TBI when compared with the reduction of casualty incidence have mainly affected car users. These results should be attributable to the improvements in standards of care, primary safety of the car fleet and general road architecture safety. However, the increased reduction in the TBI epidemics in France, when compared to those observed in other developed countries for the same periods, suggests that the effects should be strongly attributable to changes in road user behaviour induced by law enforcement. The at-risk groups for TBI after RTC are now two-wheel users (motorized or not) and individuals over 60 years of age.


Assuntos
Acidentes de Trânsito/legislação & jurisprudência , Acidentes de Trânsito/estatística & dados numéricos , Lesões Encefálicas Traumáticas/prevenção & controle , Escala de Gravidade do Ferimento , Acidentes de Trânsito/mortalidade , Adulto , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/mortalidade , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida
18.
Curr Epidemiol Rep ; 3(3): 201-211, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27547696

RESUMO

The proportions of new cancer cases and deaths that are caused by exposure to risk factors and that could be prevented are key statistics for public health policy and planning. This paper summarizes the methodologies for estimating, challenges in the analysis of, and utility of, population attributable and preventable fractions for cancers caused by major risk factors such as tobacco smoking, dietary factors, high body fat, physical inactivity, alcohol consumption, infectious agents, occupational exposure, air pollution, sun exposure, and insufficient breastfeeding. For population attributable and preventable fractions, evidence of a causal relationship between a risk factor and cancer, outcome (such as incidence and mortality), exposure distribution, relative risk, theoretical-minimum-risk, and counterfactual scenarios need to be clearly defined and congruent. Despite limitations of the methodology and the data used for estimations, the population attributable and preventable fractions are a useful tool for public health policy and planning.

19.
Public Health Nutr ; 19(2): 242-54, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25702596

RESUMO

OBJECTIVE: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. DESIGN: Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. SETTING: The European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: Women (n 334 850) from the EPIC study. RESULTS: The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in ß-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, P trend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, P trend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, P trend<0·01). CONCLUSIONS: TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.


Assuntos
Neoplasias da Mama/prevenção & controle , Dieta , Comportamento Alimentar , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Inquéritos sobre Dietas , Europa (Continente) , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
20.
J Cheminform ; 7: 52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26539250

RESUMO

BACKGROUND: In the present work, we aim to transfer to the field of virtual screening the predictiveness curve, a metric that has been advocated in clinical epidemiology. The literature describes the use of predictiveness curves to evaluate the performances of biological markers to formulate diagnoses, prognoses and assess disease risks, assess the fit of risk models, and estimate the clinical utility of a model when applied to a population. Similarly, we use logistic regression models to calculate activity probabilities related to the scores that the compounds obtained in virtual screening experiments. The predictiveness curve can provide an intuitive and graphical tool to compare the predictive power of virtual screening methods. RESULTS: Similarly to ROC curves, predictiveness curves are functions of the distribution of the scores and provide a common scale for the evaluation of virtual screening methods. Contrarily to ROC curves, the dispersion of the scores is well described by predictiveness curves. This property allows the quantification of the predictive performance of virtual screening methods on a fraction of a given molecular dataset and makes the predictiveness curve an efficient tool to address the early recognition problem. To this last end, we introduce the use of the total gain and partial total gain to quantify recognition and early recognition of active compounds attributed to the variations of the scores obtained with virtual screening methods. Additionally to its usefulness in the evaluation of virtual screening methods, predictiveness curves can be used to define optimal score thresholds for the selection of compounds to be tested experimentally in a drug discovery program. We illustrate the use of predictiveness curves as a complement to ROC on the results of a virtual screening of the Directory of Useful Decoys datasets using three different methods (Surflex-dock, ICM, Autodock Vina). CONCLUSION: The predictiveness curves cover different aspects of the predictive power of the scores, allowing a detailed evaluation of the performance of virtual screening methods. We believe predictiveness curves efficiently complete the set of tools available for the analysis of virtual screening results.

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